Zanamivir is a potent and highly selective inhibitor of the influenza virus neuraminidase. Intravenous (IV) zanamivir is being developed for treatment of hospitalized patients with influenza, especially for those patients who may be in greatest need of parenteral influenza antiviral agents. This study is a pharmacokinetic (PK) study to evaluate the safety/tolerability and pharmacokinetic profiles of IV zanamivir 300 milligrams (mg) and 600 mg in Chinese healthy subjects. Subjects will be randomized to receive either 300 mg or 600 mg IV zanamivir as a single dose followed by repeated dose every 12 hours (h) for 5 days. Subjects will be contacted or will return to study center for a follow-up visit, 7 days after the last dose or withdrawal from the study. Total number of subjects planned for enrollment will be 24 such that approximately 10 subjects complete dosing and critical assessments in each dose cohort. The total duration of the study will be approximately 6 weeks from screening to follow-up.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
24
Zanamivir will be supplied as 10 mg/mL sterile clear, colorless, aqueous solution in 20 mL clear glass vials, each containing 200 mg zanamivir. Intravenous solutions will be prepared with normal saline.
GSK Investigational Site
Shanghai, China
Composite of PK parameters of zanamivir following single dose administration
PK parameter assessed following single dose administration include the observed maximum serum drug concentration (Cmax), time to reach Cmax (tmax), elimination half-time (t1/2), area under the concentration-time curve from administration extrapolated to the last time of quantifiable concentration (AUC \[0-t\]), area under the concentration-time curve from administration extrapolated to 12 hours of quantifiable concentration (AUC \[0-12\]), area under the concentration-time curve from time zero extrapolated to infinite time (AUC \[0-infinity\]), clearance (CL) and volume of distribution after intravenous administration (Vz).
Time frame: Day 1: Pre-dose and 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h and 24 h post-dose
Composite of PK parameters of zanamivir following repeat dose administration
PK parameter assessed following repeat dose administration include Cmax, pre-dose trough concentration (Ctau), tmax, t1/2, AUC (0-t), area under the concentration-time curve during steady state (AUC \[0-tau\]), CL, Vz, volume of distribution after intravenous administration at steady state (Vss), observed accumulation ratios (Ro) and time invariance ratio (Rs).
Time frame: Day 8: Pre-dose and 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h and 24 h post-dose
Safety as assessed by the number of subjects with adverse events (AEs)
AEs will be collected from the start of study treatment and until the follow-up contact.
Time frame: Up to Day 15
Composite of clinical laboratory assessments as a measure of safety
Absolute values and change over time from pre-dose values of hematology and clinical chemistry parameters will be assessed
Time frame: Up to Day 9
Absolute values and change over time from pre-dose values of blood pressure as a measure of safety
Time frame: Up to Day 9
Absolute values and change over time from pre-dose values of pulse rate as a measure of safety
Time frame: Up to Day 9
Absolute values and change over time from pre-dose values of respiratory rate as a measure of safety
Time frame: Up to Day 9
Absolute values and change over time from pre-dose values of temperature as a safety measure
Time frame: Up to Day 9
Absolute values and change over time from pre-dose values of electrocardiogram (ECG) parameters
A 12-lead ECG will be obtained at each time point during the study and will be evaluated for safety by a qualified physician.
Time frame: Up to Day 9
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